Acute Febrile Illness In India Research Articles

Blindness as a presenting feature of leptospiral infection: A case report and review of literature

Leptospira is an emerging cause of acute febrile illness in India, which is acquired through contact of skin with contaminated water and soil. Generally, leptospirosis has mild, self-limiting course; rarely, multiple organ dysfunction can occur like aseptic meningitis (20%) and Weil’s disease (10%). Here, we report a case of bilateral optic neuritis in a girl child who presented with blindness following Leptospira infection. On ophthalmological examination, she could appreciate hand movements close to face and had afferent pupillary defect bilaterally. Fundoscopy showed normal fundus with no signs of disc edema. Magnetic resonance imaging (MRI) of brain and orbit showed bilateral hyperintensities in the optic nerve. Visual evoked potential showed prolonged latency in p100 wave in both eyes, suggestive of bilateral optic neuritis. She was diagnosed with Leptospira infection with aseptic meningitis and retrobulbar optic neuritis. She was treated conservatively. She responded well with improvement of visual acuity to 6/6 at the time of discharge.

Procalcitonin Levels for Prognosis of Scrub Typhus Patients: A Retrospective Observational Analysis from a Tertiary Care Centre in Northern India

Introduction: Scrub typhus is a major cause of acute febrile illness in India. It presents with various clinical features that vary from fever to multiorgan dysfunction. Similar symptoms and presentations cause difficulty in diagnosis. Therefore, it is important to have early and prompt diagnosis with better prognostic markers to decrease morbidity and mortality. Aim: To determine the prognosis of scrub typhus patients based on the Procalcitonin (PCT) levels. Materials and Methods: This retrospective observational study was conducted in the Microbiology Department of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, India, from January 2022 to January 2023. A total of 120 patients admitted to the hospital, who tested positive for Scrub typhus IgM by ELISA during this period and had a negative blood culture, were included in this study. Data analysis was conducted from February 2023 to April 2023. PCT levels of all these patients at the time of admission were recorded. The demographic information, laboratory parameters, and treatment regimen of these patients were also compiled. Statistical analysis was performed, and p-value was used to determine statistical significance. Results: The majority of the patients belonged to the age group of 21-40 years. Among these, elevated PCT values (ranging from 0.05-89.4 ng/mL) were observed in 112 (93.33%) patients. Twelve (10%) patients died during the study period, and all of them had elevated PCT levels. Among these, six developed septic shock with Multiple Organ Dysfunction Syndrome (MODS). Increased leukocyte values, elevated liver enzymes such as Aspartate Aminotransferase (SGOT/AST) and Alanine Transferase (SGPT/ALT), abnormal coagulation profile, and abnormal renal profile with elevated urea and uric acid levels were found to be significantly associated with scrub typhus patients with elevated PCT values. Conclusion: There is a need to address the role of prognostic markers in the management of scrub typhus patients. This may lead to breakthroughs in the field of diagnostic research and help improve the prognosis of these patients.

Mite Bite Underlying A Lid Swelling - A Rare Presentation Of Scrub Typhus

Scrub Typhus, a vector-borne and zoonotic disease by Orientia tsutsugamushi, is one of the causes of acute febrileillness in India. In endemic regions where Scrub Typhus is prevalent, healthcare providers should keep an eye out and be verysuspicious about this disease, especially when encountering patients with acute febrile illness and exposure to mite-infested areas.Prompt recognition and appropriate diagnostic testing, such as serological assays or molecular methods, are essential for accuratediagnosis. Once diagnosed, treatment with appropriate antibiotics, such as doxycycline or azithromycin, can effectively manageScrub Typhus and prevent complications. Early initiation of treatment is crucial to reduce the chance of severe disease and potentialmortality. This case report highlights the importance of considering Scrub Typhus as a potential differential diagnosis in lid infectionsand acute febrile illnesses, particularly in areas where the disease is endemic. Healthcare providers should be aware of the diverseclinical presentations and remain vigilant to ensure timely and accurate diagnosis, leading to appropriate management and improvedpatient outcomes. Public health efforts should also focus on increasing awareness about Scrub Typhus, its prevention, and earlydetection to minimize the burden of this often underdiagnosed disease. In this case report, we presented a child with febrile illnessand unilateral lid swelling misdiagnosed as stye. The presence of eschar prompted an investigation of Scrub typhus, which waspositive. This case is reported as the lid is an unusual site for eschar formation. To reiterate, scrub typhus should be considered adifferential diagnosis in lid infections and acute febrile illness, particularly in endemic areas.

Leptospirosis and Scrub Typhus Coinfection of a 50-year-old male: A Case study

The bacterial diseases, leptospirosis and scrub typhus are important causes of acute febrile illness in India and are responsible for high morbidity and mortality. The common epidemiology of the zoonotic diseases creates an opportunity of dual infection. In this study, we describe a medical case of a 50-year-old male who was reported to have high grade fever for 10 days along with chills and coughs and was admitted to the RG Kar Medical College and Hospital on November last year. He was reported to suffer from conjunctival congestion, episode of pr bleeding, bowel and bladder incontinence, abdominal distension and pedal edema. Enzyme linked immunosorbent assay (ELISA) detected IgM antibodies to both leptospirosis and scrub typhus in the serum of the patient indicating dual infection with both bacterial diseases. Timely diagnosis of the patient followed by treatment with the antibiotics and associated medication resulted in complete recovery from both the diseases. As both leptospirosis and scrub typhus present with similar clinical features, co-infection of these two diseases is not uncommon. Cases of dual infections must be therefore considered seriously and choice of therapy should include those drugs that cover for both the infections.

Recent cases of co-infection of scrub typhus and leptospirosis: A short clinical study

Scrub typhus and leptospirosis are bacterial zoonotic diseases causing high morbidity and mortality. Both are important causes of acute febrile illness in India. The common epidemiology of both the diseases creates an opportunity of dual infections with these diseases. The present study was conducted at RG Kar Medical College and Hospital to determine simultaneous infection of leptospirosis and scrub typhus in sera of febrile patients and evaluate the cases of serological dual infections. IgM antibodies to both leptospira and scrub typhus were detected by Enzyme linked immunosorbant assay (ELISA). During the study period (August 2022-October 2022), serum samples of patients were received for serology for scrub typhus. Out of these samples, 5 patients diagnosed for scrub typhus infection also had IgM antibodies to leptospira, thus indicating co-infection of both diseases. The current study adds further to few previously published reports on co-infection of scrub typhus with leptospirosis. As both leptospirosis and scrub typhus present with similar clinical features, co-infection of these two diseases is not uncommon and requires further confirmation at molecular level. Accordingly, cases of dual infections must be considered seriously and choice of therapy should include those drugs that cover for both the infections.

The burden of scrub typhus in India: A systematic review.

BackgroundScrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India.MethodologyWe performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies.Principal findingsIn the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%.Conclusion/significanceScrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed.

Eschar and IgM ELISA in the Diagnosis of Scrub Typhus

AbstractScrub typhus is one of the leading causes of acute febrile illness in India. This study aimed to determine the best diagnostic tool for the identification of scrub typhus and study the possible association between diagnostics and clinical characteristics. Patients with fever of ≤15 days admitted to the hospital satisfying the case definition of 47 kDa quantitative polymerase chain reaction (qPCR) positivity OR scrub typhus IgM ELISA positivity along with the presence of eschar OR Scrub typhus IgM ELISA positivity along with defervescence of fever within 72 h of initiation of specific therapy were recruited. Of the 116 patients satisfying the case definition, 47 kDa qPCR was positive in 43 (37%) patients, whereas IgM ELISA was positive in 104 (90%) patients and eschar was seen in 59 (51%) patients. The median duration of fever was 7.5 days (interquartile range 6–10 days). Multiorgan dysfunction syndrome (MODS) was described in 44 (37.9%) patients. Two patients (1.8%) succumbed to the illness. Presence of eschar and IgM ELISA positivity were detected in 106 (91%) cases. Scrub typhus, even with MODS, has low mortality because of immediate institution of specific therapy due to physician awareness. The presence of eschar and IgM ELISA positivity can be used to detect a majority of cases of scrub typhus.

Incidence of scrub typhus in a tertiary care hospital in Kolkata, India

Background: Authors aimed to identify incidence of scrub typhus among patients of fever. Scrub typhus is an endemic disease in India caused by Orientia tsutsugamushi, transmitted by trombiculid mites. It is an important cause of acute febrile illness in India. Signs and symptoms include fever, headache, myalgia and GI symptoms and is generally associated with morbilliform rash (<40%), eschar (<50%) which is due to bite of the mite. Abnormal LFTs and lymphocytosis are commonly seen in early phase of illness. It’s often labelled as PUO. Early diagnosis and prompt administration of therapy mostly leads to complete recoveryMethods: Authors screened 100 patients presenting with fever, malaise, headache, with or without rash for more than a week from the month of May to December 2019. Routine blood investigations with fever profile (Dengue NS1 antigen, MP, MPDA, TyphidotM) and cultures were done. Patients in whom no cause of fever could be established, having lymphocytosis, hyponatremia and transaminitis, they were tested for Scrub typhus by using Indirect immunofluorescence & detection of IgM antibody.Results: Total 22 patients were found positive for scrub typhus by using the aforementioned method (22%). Male: Female ratio was 3:4 (9 vs 12). Patients were in the age group of 16-76 years. Lymphocytosis, hyponatremia and transaminitis were cardinal features seen in almost all patients diagnosed with Scrub Typhus.Conclusions: This study will help clinicians to have a stronger suspicion of scrub typhus in undiagnosed febrile patients.

Rickettsial Diseases: Not Uncommon Causes of Acute Febrile Illness in India.

Rickettsial diseases (RDs) are major under-diagnosed causes of arthropod borne acute febrile illness (AFI) presenting with a range of symptoms from mild self-limiting fever to fatal sepsis. The spotted fever group (SFG) and typhus group (TG) are major RDs, which are commonly caused by Rickettsia conorii and Rickettsia typhi, respectively. The limited availability and role of serological tests in the acute phase of illness warrants rapid reliable molecular methods for diagnosis and epidemiological studies. Two hundred patients with AFI in whom the routine fever diagnostics were negative, were enrolled over a period of two months (April 2019 to May 2019). DNA was extracted and in-house nested PCR using primers specific for both SPG and TG pathogens was used. The positive amplified products were sequenced for species identification and phylogenetic analysis was performed using MEGA 7.0.14 software (iGEM, Temple University, Philadelphia, PA 19122, USA). The demographic details of the RD cases were documented. The prevalence of RD among AFI cases was 7% (14/200); SFG and TG were identified as the cause in 4% and 3% of AFI cases, respectively. The median age of the RD cases was 22 years (range 2–65). The median duration of fever was 3 days (range 1–12). The RD cases presented with respiratory symptoms or signs (44.44%), jaundice (22.22%), abdominal pain (22.22%), diarrhea (22.22), vesicular rash (11.11%), vomiting (11.11%), loss of appetite (11.11%), headache (11.11%), leukocytosis (88.88% with mean count 22,750/mm3), and thrombocytopenia (33.33%). The cases were treated empirically with piperacillin-tazobactam (66.66%), clindamycin (44.44%), cefotaxime (33.33%), meropenem (33.33%), metronidazole (33.33%), doxycycline (22.22%), azithromycin (22.22%), ceftriaxone (11.11%), and amoxicillin-clavulanic acid (11.11%). The mortality among the RD cases was 11.11%. The present pilot study shows that RD is not an uncommon cause of AFI in north India. The febrile episodes are usually transient, not severe and associated with heterogenous clinical presentation without documented history of tick exposure in the hospitalized patients. The transient, non-severe, febrile illness could be due to transient rickettsemia resulting from empirical antimicrobial therapy as the rickettsial organisms are expected to be more susceptible to higher doses of β-lactam antibiotics. The study emphasizes the molecular method as a useful tool to identify rickettsial etiology in AFI.

Molecular confirmation & characterization of Rickettsia conorii in north India: A report of three cases.

Background & objectives:In India, spotted fever group rickettsiae (SFGR) are an underdiagnosed cause of acute febrile illness (AFI). The non-specific Weil-Felix test is the first diagnostic modality for the diagnosis of SFGR in many laboratories due to the lack of advanced diagnostic facilities in developing countries. The aim of this study was to detect SFGR using molecular methods in the patients, presenting with AFI in a tertiary care centre in north India.Methods:Consecutive patients (>14 yr of age) with AFI were enrolled over a six month period. Standard investigations for common pathogens causing AFI in India (malaria, dengue, scrub typhus, leptospirosis and enteric fever) were carried out. In patients who were negative for all of the above investigations, blood was subjected to polymerase chain reaction (PCR) targeting outer membrane protein A (ompA) gene of Rickettsia.Results:Of the 51 patients with an undiagnosed aetiology, three were positive by ompA PCR. Two of the PCR products produced good sequences and BLAST identification confirmed them as Rickettsia conorii. The sequences of R. conorii reported from south India clustered with two previously reported novel rickettsial genotypes. The study sequences clustered in a group different from that of Rickettsia spp. of the south Indian sequences reported earlier.Interpretation & conclusions:This study showed the existence of R. conorii in north India. Testing for SFGR may be included in the diagnostic workup of AFI for better disease management.

Phylogenetic Diversity of Orientia tsutsugamushi Isolates in Patients with Scrub Typhus in Bengaluru, India

AbstractScrub typhus has re-emerged as an important cause of acute febrile illness in India. There is a dearth of information on strain diversity of Orientia tsutsugamushi from Karnataka, India, hence the present study sought to address this issue. One hundred clinically suspected cases of scrub typhus/rickettsiosis (as per the DHR-ICMR guidelines) were included. Nested-polymerase chain reaction (PCR) for 56-kDa gene and phylogenetic analysis was performed. PCR was positive in 22 cases and phylogenetic analysis showed the presence of different strains, with predominance of clustering (57%) with Gilliam-type for the first time in Karnataka. Knowledge of genetic diversity has implications in development of diagnostics and vaccine.

Genetic diversity of Orientia tsutsugamushi strains from patients in north India

BackgroundScrub typhus has emerged as a major cause of acute febrile illness in India in recent years. The causative agent, Orientia tsutsugamushi has more than 20 prototype strains due to a variable 56-kDa outer membrane protein. It is crucial to know the prevailing types in India for the success of diagnostic immunoassays and prospective vaccine candidates. In north India, the principal types circulating are largely unknown. Our tertiary care hospital caters to a large area of north India (around 7 states and one union territory). Therefore, the current study was planned to identify the genotypes of O. tsutsugamushi strains circulating in this wide area of north India. Materials and methodsAdults and children presenting with suspected scrub typhus between July 2013 and December 2013 were included in this study. DNA was extracted from whole blood and a nested PCR was used to amplify a 483-bp region of the 56-kDa antigen gene of O. tsutsugamushi. The PCR products were purified and DNA sequencing was performed and aligned using the CLUSTAL_X2 program. A phylogenetic tree was constructed using neighbour- joining algorithms and analysed using the sequences obtained in this study and those obtained from the GenBank database. ResultsA total of 34 samples were positive for PCR. The amplicons were sequenced and analyzed. Karp-like strains predominated in all states studied (64.7%) followed by Gilliam-like (26.47 %) and 8.82% similar to Hualien 1 or S072. We did not find any Kato or Kawasaki-like strain. Karp like strains showed >99% similarity to TH2033, TH2191, TH2208, Xinjiang & Neimeng strains and Gilliam-like strains showed >99% similarity to Clone ISS -11. ConclusionOrientia tsutsugamushi shows a great diversity in its strains over a large geographical area of north India. This has implications in the production of both diagnostic assays and vaccine for scrub typhus.

Eschar and IgM ELISA in the diagnosis of scrub typhus.

Scrub typhus is one of the leading causes of acute febrile illness in India. This study aimed to determine the best diagnostic tool for the identification of scrub typhus and study the possible association between diagnostics and clinical characteristics. Patients with fever of ≤15 days admitted to the hospital satisfying the case definition of 47 kDa quantitative polymerase chain reaction (qPCR) positivity OR scrub typhus IgM ELISA positivity along with the presence of eschar OR Scrub typhus IgM ELISA positivity along with defervescence of fever within 72 h of initiation of specific therapy were recruited. Of the 116 patients satisfying the case definition, 47 kDa qPCR was positive in 43 (37%) patients, whereas IgM ELISA was positive in 104 (90%) patients and eschar was seen in 59 (51%) patients. The median duration of fever was 7.5 days (interquartile range 6-10 days). Multiorgan dysfunction syndrome (MODS) was described in 44 (37.9%) patients. Two patients (1.8%) succumbed to the illness. Presence of eschar and IgM ELISA positivity were detected in 106 (91%) cases. Scrub typhus, even with MODS, has low mortality because of immediate institution of specific therapy due to physician awareness. The presence of eschar and IgM ELISA positivity can be used to detect a majority of cases of scrub typhus.

Vector-Borne Disease is a Common Cause of Hospitalized Febrile Illness in India.

Acute febrile illness (AFI) is a major cause of morbidity and mortality in India and other resource-limited settings, yet systematic etiologic characterization of AFI has been limited. We prospectively enrolled adults (N = 970) and children (age 6 months to 12 years, N = 755) admitted with fever from the community to Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We systematically obtained a standardized clinical history, basic laboratory testing, and microbiologic diagnostics on enrolled participants. Results from additional testing ordered by treating clinicians were also recorded. A microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met standardized case definitions for pneumonia and meningitis without an identified organism; 559 (32%) were assigned a clinical diagnosis in the absence of a confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were the most common cause of AFI in adults including dengue (N = 188, 19%), malaria (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In children, pneumonia was the most common cause of AFI (N = 214, 28%) and death. Bacteremia was found in 68 (4%) participants. Central nervous system infections occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is diverse, highly seasonal, and difficult to differentiate on clinical grounds alone. Diagnostic strategies adapted for season and age may reduce diagnostic uncertainty and identify causative organisms in treatable, fatal causes of AFI.

High Burden of Antimicrobial Resistance and Mortality Among Adults and Children With Community-Onset Bacterial Infections in India.

In India, antimicrobial consumption is high, yet systematically collected data on the epidemiology, risk factors, and outcomes of antimicrobial-resistant infections are limited. A prospective study of adults and children hospitalized for acute febrile illness was conducted between August 2013 and December 2015. In-hospital outcomes were recorded, and logistic regression was performed to identify independent predictors of community-onset antimicrobial-resistant infections. Among 1524 patients hospitalized with acute febrile illness, 133 isolates were found among 115 patients with community-onset infections; 66 isolates (50.0%) were multidrug resistant and, of 33 isolates tested for carbapenem susceptibility, 12 (36%) were resistant. Multidrug-resistant infections were associated with recent antecedent antibiotic use (adjusted odds ratio [aOR], 4.17; 95% confidence interval [CI], 1.19-19.7) and were independently associated with mortality (aOR, 6.06; 95% CI, 1.2-55.7). We found a high burden of community-onset antimicrobial-resistant infection among patients with acute febrile illness in India. Multidrug-resistant infection was associated with prior antibiotic use and an increased risk of mortality.

Scrub typhus in pregnancy: Maternal and fetal outcomes.

Scrub typhus is an important unrecognized cause for undifferentiated acute febrile illness in India associated with poor fetal outcomes. Maternal and fetal outcomes among pregnant patients with scrub typhus presenting to a tertiary care university teaching hospital from January 2010 to July 2012 were studied. Scrub typhus was diagnosed by clinical criteria along with scrub ELISA positivity or an eschar. In total, 33 of 738 patients (4.5%) who were diagnosed with scrub typhus were pregnant; 57.6% were in the third trimester, 27.3% in the second, and only 15.2% in the first trimester; 69.7% required admission to intensive care. Mortality was low (3%, n = 1) compared to 12.2% mortality reported previously. All patients were treated with Azithromycin. Poor fetal outcome was observed in 51.5% of these pregnancies with fetal loss occurring in 42.4% and preterm childbirth in 9.1%. Scrub typhus complicating pregnancy is associated with a poor fetal outcome despite treatment with Azithromycin. A majority require intensive care treatment for survival.

Scrub Typhus and Leptospirosis: The fallacy of Diagnosing with IgM Enzyme Linked Immunosorbant Assay

Introduction: Leptospirosis and scrub typhus are important causes of acute febrile illness in India. IgM Enzyme Linked Immunosorbant Assay (ELISA) is the most common diagnostic modality used for their diagnosis. The common epidemiology of both the diseases creates an opportunity of dual infections with these diseases. Therefore, the objective of the study was to detect and evaluate the cases of serological and molecular dual infections. Methodology: A cross sectional diagnostic study from October 2013 to October 2015 was conducted on 258 patients with acute febrile illness. All the samples were subjected to IgM ELISA for scrub typhus and leptospirosis. The samples that were positive for both scrub typhus and leptospirosis were subjected to serological tests for other infections. They were also subjected to PCR assays to find out the cases of molecular dual infections. Results: A total of twenty serum samples were positive by IgM ELISA for leptospirosis while thirty five serum samples were positive by IgM ELISA for scrub typhus. Among these, ten samples were positive for both the serological tests. These dual positives were additionally positive by serology for some other infections [Dengue (n = 2), Mycoplasma pneumoniae (n = 1), Malaria (n = 1), Chlamydia pneumoniae (n = 6), Typhoid (n = 2) and Legionella pneumophila (n = 1)]. Only one case of molecular dual infection was confirmed. Conclusion: The possibility of serological co-infections should be investigated in endemic areas. In a case of serological dual infection, since there are high chances of serological cross reactivity, molecular confirmation should be sought for. The choice of therapy in inconclusive cases should include those drugs that cover for both the infections.

Scrub Typhus Seroprevalence in Healthy Indian Population.

Scrub typhus, a zoonosis caused by Orientia tsutsugamushi, is an important cause of acute febrile illness in India. This preliminary study determines the seroprevalence of scrub typhus in healthy Indian adults by measuring IgM and IgG antibodies to scrub typhus by ELISA in 100 healthy blood donors. Our study demonstrates a 15% seroprevalence of scrub typhus in adults. Further studies are needed to confirm these findings especially in children.